title: In silico study of structural and geometrical requirements of natural sesquiterpene lactones with trypanocidal activity.
abstract: Chagas' disease, caused by the intracellular protozoan Trypanosoma cruzi, is one of the most serious health problems throughout South America. Despite the progress that has been made in the study of its biochemistry and physiology, more efficient chemotherapies to control this parasitic infection are still lacking. In this paper we report the trypanocidal and cytotoxic activities of a series of sesquiterpene lactones, isolated from Asteraceae medicinal plants. The significant trypanocidal activity and high selectivity indexes found for many of the compounds evaluated, prompted us to undertake a quantitative structure-activity relationship study. A model using 3D molecular descriptors allowed us to set up a high correlation of the observed activity and the atomic spatial arrangement of these sesquiterpene lactones closely related to steric parameters.
authors.forename: L
authors.initials: L
authors.lastname: Fabian
authors.forename: V
authors.initials: V
authors.lastname: Sulsen
authors.forename: F
authors.initials: F
authors.lastname: Frank
authors.forename: S
authors.initials: S
authors.lastname: Cazorla
authors.forename: E
authors.initials: E
authors.lastname: Malchiodi
authors.forename: V
authors.initials: V
authors.lastname: Martino
authors.forename: E
authors.initials: E
authors.lastname: Lizarraga
authors.forename: C
authors.initials: C
authors.lastname: Catalán
authors.forename: A
authors.initials: A
authors.lastname: Moglioni
authors.forename: L
authors.initials: L
authors.lastname: Muschietti
authors.affiliation: Catedra de Farmacognosia- IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquimica, UBA. ccatalan@fbqf.unt.edu.ar.
authors.forename: L
authors.initials: L
authors.lastname: Finkielsztein
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D001688:Biological Products; D007783:Lactones; D012717:Sesquiterpenes; D014344:Trypanocidal Agents